Syntheses and characterization of titanium malonato and amino acid complexes: [Ti(cp)2(OOCCH2NMe2)] - The first structurally characterized α-amino acid titanium(III) complex

The reaction of [Ti(cp^∗)₂(BTMSA)] (1) (cp^∗ = η⁵-C₅Me₅, BTMSA = bis(trimethylsilyl)acetylene) with malonic acids ((HOOC)₂CR₂, R = H, Me) and N,N-dimethylglycine resulted in the formation of titanium(IV) dicarboxylato complexes [Ti(cp^∗)₂{(OOC)₂CR₂}] (R = H, 2; R = Me, 3) and an α-amino acid titanium(III) complex [Ti(cp^∗)₂(OOCCH₂NMe₂)] (4). The identities of complexes 2-4 were confirmed by microanalysis, ¹H and ¹³C NMR spectroscopy (2, 3), ESI-MS and CID experiments (2, 3) as well as by ESR and magnetic measurements (μ_eff = 1.81, 298 K) for 4. Single X-ray diffraction analyses of 2 and 4 exhibited monomolecular complexes in which the titanium atom is distorted tetrahedrally coordinated by two η⁵-C₅Me₅ rings and by the chelating bound malonato-κ²O,O′ (2) and N,N-dimethylglycinato-κ²O,O′ ligand (4).     

Carboxy-derived (tpy)2Ru complexes as sub-units in supramolecular architectures: The solubilized ligand 4′-(4-carboxyphenyl)-4,4″-di-(tert-butyl)tpy and its homoleptic Ru(II) complex

We herein describe the synthesis and characterization of a series of homoleptic, Ru(II) complexes bearing peripheral carboxylic acid functionality based upon the novel ligand 4′-(4-carboxyphenyl)-4,4″-di-(tert-butyl)tpy (L₁), as well as 4′-(4-carboxyphenyl)tpy (L₂) and 4′-(carboxy)tpy (L₃) (where tpy = 2,2′: 6′,2″-terpyridine). Inspection of the metal-based oxidations (E_1/2 = 1.22-1.42 V) indicates an anodic shift (∼0.2 V) for (L₃)₂Ru²⁺ (3b) (E_1/2 = 1.40 V) relative to (L₂)₂Ru²⁺ (2b) (E_1/2 = 1.22 V). The metal-based oxidation (E_1/2 = 1.22 V) and ligand-based reductions (E_1/2 = −1.25 to −1.52 V) of (L₁)₂Ru²⁺ (1) are essentially invariant relative to those of the structural analogue 2b (PF₆)₂, which suggests no significant electronic effect caused by the tert-butyl groups. This is supported by invariance in the metal-to-ligand charge transfer bands in both the electronic absorption (494-489 nm) and emission spectra (654-652 nm). However, contrary to 2b, complex 1 is both very soluble and exhibits a highly porous solid-state structure with internal cavity dimensions of 15 Å × 14 Å due to the preclusion of inter-annular interactions by the bulky tert-butyl substituents.     

Luminescent probes for indole-binding proteins derived from ruthenium(II) polypyridine complexes

We report here the synthesis, characterisation, electrochemical, photophysical and protein-binding properties of four luminescent ruthenium(II) polypyridine indole complexes [Ru(bpy)₂(L1)](PF₆)₂ (1), [Ru(bpy)₂(L2)](PF₆)₂ (2), [Ru(L1)₃](PF₆)₂ (1a), and [Ru(L2)₃](PF₆)₂ (2a) (bpy = 2,2′-bipyridine; L1 = 4-(N-(2-indol-3-ylethyl)amido)-4′-methyl-2,2′-bipyridine; L2 = 4-(N-(6-N-(2-indol-3-ylethyl)hexanamidyl)amido)-4′-methyl-2,2′-bipyridine). Their indole-free counterparts, [Ru(bpy)₂(L3)](PF₆)₂ (3) and [Ru(L3)₃](PF₆)₂ (3a) (L3 = 4-(N-(ethyl)amido)-4′-methyl-2,2′-bipyridine), have also been synthesised for comparison purposes. Cyclic voltammetric studies revealed ruthenium-based oxidation at ca. +1.3 V versus SCE and diimine-based reductions at ca. −1.20 to −2.28 V. The indole moieties of complexes 1, 2, 1a and 2a displayed an irreversible wave at ca. +1.1 V versus SCE. All the ruthenium(II) complexes exhibited intense and long-lived orange-red triplet metal-to-ligand charge-transfer ³MLCT (dπ(Ru) → π*(L1-L3)) luminescence upon visible-light irradiation in fluid solutions at 298 K and in alcohol glass at 77 K. The binding of the indole-containing complexes to bovine serum album (BSA) has been studied by quenching experiments and emission titrations.     

Synthesis and antitubercular evaluation of amidoalkyl dibenzofuranols and 1H-benzo[2,3]benzofuro[4,5-e][1,3]oxazin-3(2H)-ones

A new class of amidoalkyl dibenzofuranols and 1H-benzo[2,3]benzofuro[4,5-e][1,3]oxazin-3(2H)-ones was synthesized in very good yields through polyphosphoric acid supported on silica (PPA-SiO₂) catalyzed one-pot three component condensation of 2-dibenzofuranol; aromatic aldehydes and acetamide or benzamide or urea under solvent free conditions. At 125 °C the reaction led to the formation of amidoalkyl dibenzofuranols 5a-k where as at 160 °C cyclization take place to give oxazin-3(2H)-one analogues 6a-e. Screening all the 16 compounds for in vitro antimycobacterial activity against Mycobacterium tuberculosis H37Rv (MTB) resulted 1-((4-chlorophenyl)(2-hydroxydibenzo[b,d]furanyl)methyl)urea 5h; 1-((4-bromophenyl)(2-hydroxydibenzo[b,d]furanyl)methyl)urea 5i; 1-phenyl-1H-benzo[2,3]benzo furo[4,5-e][1,3]oxazin-3(2H)-one 6a (MIC 3.13 μg/mL) and 1-(4-chlorophenyl)-1H-benzo[2,3]benzofuro[4,5-e][1,3]oxazin-3(2H)-one 6b; 1-(4-bromophenyl)-1H-benzo[2,3]benzofuro [4,5-e][1,3]oxazin-3(2H)-one 6c (MIC 1.56 μg/mL) as most active antitubercular agents.     

Synthesis and exploratory coordination chemistry of the new ditertiary carbinamine ligand 2,6-bis(α-aminoisopropyl)pyridine

The new pyridine-based N∩N∩N tridentate ligand 2,6-C₅H₃N(CMe₂NH₂)₂ (1) was synthesized by the treatment of 2,6-pyridinedicarbonitrile with an excess of the organocerium reagent in situ generated from CeCl₃ and methyllithium in THF. The reaction of 1 with [RuCl₂(PPh₃)₃] in THF at ambient conditions afforded (OC-6-23)-[RuCl{2,6-C₅H₃N(CMe₂NH₂)₂}(PPh₃)₂]Cl (2). The corresponding dimethyl sulfoxide complex [RuCl{2,6-C₅H₃N(CMe₂NH₂)₂}{S(O)Me₂}₂]Cl (3) was isolated as a mixture of the (OC-6-23) and (OC-6-32) stereoisomers 3a and 3b from the reaction between 1 and (OC-6-22)-[RuCl₂{S(O)Me₂}₃(OSMe₂)] in toluene at 80 °C. A prolonged interaction in toluene at reflux temperature gave isomerically pure 3a. The metal trichloride hydrates MCl₃ · xH₂O (M = Ru, Rh, Ir; x ≅ 2-4) produced mer-[RuCl₃{2,6-C₅H₃N(CMe₂NH₂)₂}] (M = Ru: 4; Rh: 5; Ir: 6), when combined with 1 in refluxing ethanol. The crystal structures of the following compounds were determined: ligand 1 and complexes 2-5 as addition compounds 2 · CH₂Cl₂, 3a · C₇H₈, 4 · EtOH and .     

β-Diiminatolanthanoid(III) halides revisited

The crystalline compounds [LnCl₂(L)(thf)₂] [Ln = Ce (1), Tb (2), Yb (3)], [NdI₂(L)(thf)₂] (4), [LnCl(L′)₂] [Ln = Tb (5), Yb (6) (a known compound)] and [YbCl(L′′)(μ-Cl)₂Li(OEt₂)₂] (7) have been prepared [L = {N(C₆H₃Prⁱ₂-2,6)C(H)}₂CPh, L′ = {N(SiMe₃)C(Ph)}₂CH, L′′ = {N(SiMe₃)C(C₆H₄Ph-4)}₂CH]. The X-ray molecular structures of 2-7 have been established; in each, the monoanionic ligand L, L′ or L′′ is N,N′-chelating and essentially π-delocalised. Each of 1-7 was prepared from the appropriate LnCl₃, or for 4 [NdI₃(thf)₂], and an equivalent portion of the appropriate alkali metal [Li for 7, Na for 2, 3 and 5, or K for 1, 4 and 6] β-diiminate in thf; the isolation of exclusively 5 and 6 (rather than the L′ analogues of 2 or 3) is noteworthy, as is the structure of 7 which has no precedent in Group 3 or 4f metal β-diiminato chemistry.     

New class of acetylcholinesterase inhibitors from the stem bark of Knema laurina and their structural insights

Bioassay-guided extraction of the stem bark of Knema laurina showed the acetylcholinesterase (AChE) inhibitory activity of DCM and hexane fractions. Further repeated column chromatography of hexane and DCM fractions resulted in the isolation and purification of five alkenyl phenol and salicylic acid derivatives. New compounds, (+)-2-hydroxy-6-(10′-hydroxypentadec-8′(E)-enyl)benzoic acid (1) and 3-pentadec-10′(Z)-enylphenol (2), along with known 3-heptadec-10′(Z)-enylphenol (3), 2-hydroxy-6-(pentadec-10′(Z)-enyl)benzoic acid (4), and 2-hydroxy-6-(10′(Z)-heptadecenyl)benzoic acid (5) were isolated from the stem bark of this plant. Compounds (1-5) were tested for their acetylcholinesterase inhibitory activity. The structures of these compounds were elucidated by the 1D and 2D NMR spectroscopy, mass spectrometry and chemical derivatizations. Compound 5 showed strong acetylcholinesterase inhibitory activity with IC₅₀ of 0.573 ± 0.0260 μM. Docking studies of compound 5 indicated that the phenolic compound with an elongated side chain could possibly penetrate deep into the active site of the enzyme and arrange itself through π-π interaction, H-bonding, and hydrophobic contacts with some critical residues along the complex geometry of the active gorge.     

Bioactive saponins from Microsechium helleri and Sicyos bulbosus

Eleven oleanane-type saponins (1-11) have been isolated from Microsechium helleri and Sicyos bulbosus roots and were evaluated for their antifeedant, nematicidal and phytotoxic activities. Saponins {3-O-β-d-glucopyranosyl (1 → 3)-β-d-glucopyranosyl-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-xylopyranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranoside} (1), and {3-O-β-d-glucopyranosyl-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-α-l-rhamnopyranosyl-(1 → 3)-β-d-xylopyranosyl-(1 → 4)-[β-d-xylopyranosyl-(1 → 3)]-α-l-rhamnopyranosyl-(1 → 2)-α-l-arabinopyranoside} (2) were also isolated from M. helleri roots together with the two known compounds 3 and 4. Seven known structurally related saponins (5-11) were isolated from S. bulbosus roots. The structures of these compounds were established as bayogenin and polygalacic glycosides using one- and two-dimensional NMR spectroscopy and mass spectrometry. Compounds 7, 10, bayogenin (12) and polygalacic acid (13) showed significant (p < 0.05) postingestive effects on Spodoptera littoralis larvae, compounds 5-11 and 12 showed variable nematicidal effects on Meloydogyne javanica and all tested saponins had variable phytotoxic effects on several plant species (Lycopersicum esculentum, Lolium perenne and Lactuca sativa). These are promising results in the search for natural pesticides from the Cucurbitaceae family.     

Four new steroidal glycosides from Solanum torvum and their cytotoxic activities

Two novel C-22 steroidal lactone saponins, namely solanolactosides A, B (1, 2) and two new spirostanol glycosides, namely torvosides M, N (3, 4) were isolated from ethanol extract of aerial parts of Solanum torvum. Their structures were characterized as solanolide 6-O-[α-l-rhamnopyranosyl-(1 → 3)-O-β-d-quinovopyranoside] (1), solanolide 6-O-[β-d-xylopyranosyl-(1 → 3)-O-β-d-quinovopyranoside] (2), yamogenin 3-O-[β-d-glucopyranosyl-(1 → 6)-O-β-d-glucopyranoside] (3) and neochlorogenin 3-O-[β-d-glucopyranosyl-(1 → 6)-O-β-d-glucopyranoside] (4) on the basis of spectroscopic analysis. The cytotoxicities of the saponins (1-4) were evaluated in vitro against a panel of human cancer cell lines. Compounds 3 and 4 showed significant cytotoxic activity with the cell lines.     

Syntheses and 1D structures of organic-inorganic hydrid polymers combining M(ClO4)2 (M = Cd, Zn) junctions and the semi-flexible bis-pyridyl ligand 3-pmpmd (N,N′-bis(3-pyridylmethyl)pyromellitic diimide)

Two 1D organic-inorganic coordination polymers, [Cd(3-pmpmd)(CH₃CN)₂(H₂O)₂]_n · 2n(ClO₄)₂ (1) and [Zn(3-pmpmd)_1.5(H₂O)₂]_n · 2n(ClO₄)₂ · nCH₃CN (2), were obtained from M(ClO₄)₂ (M = Cd, Zn) and the semi-flexible 3,3′-N-donor bis-pyridyl ligand 3-pmpmd: 1 has an 1D zigzag framework with 3-pmpmd in the Z_T-mode (anti, trans-) conformation, while 2 has an 1D rod and loop network with 3-pmpmd in both Z_T- and Z_C-mode (anti, cis-) conformations. Results showed that the metal ions could influence the coordination mode of a semi-flexible bis-pyridyl ligand.     

Fellutamide B is a potent inhibitor of the Mycobacterium tuberculosis proteasome

Via high-throughput screening of a natural compound library, we have identified a lipopeptide aldehyde, fellutamide B (1), as the most potent inhibitor of the Mycobacterium tuberculosis (Mtb) proteasome tested to date. Kinetic studies reveal that 1 inhibits both Mtb and human proteasomes in a time-dependent manner under steady-state condition. Remarkably, 1 inhibits the Mtb proteasome in a single-step binding mechanism with K_i = 6.8 nM, whereas it inhibits the human proteasome β5 active site following a two-step mechanism with K_i = 11.5 nM and  = 0.93 nM. Co-crystallization of 1 bound to the Mtb proteasome revealed a structural basis for the tight binding of 1 to the active sites of the Mtb proteasome. The hemiacetal group of 1 in the Mtb proteasome takes the (R)-configuration, whereas in the yeast proteasome it takes the (S)-configuration, indicating that the pre-chiral CHO group of 1 binds to the active site Thr1 in a different orientation. Re-examination of the structure of the yeast proteasome in complex with 1 showed significant conformational changes at the substrate-binding cleft along the active site. These structural differences are consistent with the different kinetic mechanisms of 1 against Mtb and human proteasomes.     

Synthesis, characterization and in vitro cytotoxicity of the first palladium(II) oxalato complexes involving adenine-based ligands

The first [Pd(Lⁿ)₂(ox)] xH₂O oxalato(ox) complexes involving 2-chloro-N6-(benzyl)-9-isopropyladenine (L¹; complex 1), 2-chloro-N6-(4-methoxybenzyl)-9-isopropyladenine (L²; 2), 2-chloro-N6-(2,3-dimethoxybenzyl)-9-isopropyladenine (L³; 3), 2-chloro-N6-(2,4-dimethoxybenzyl)-9-isopropyladenine (L⁴; 4), and 2-chloro-N6-(4-methylbenzyl)-9-isopropyladenine (L⁵; 5) have been synthesized by the reactions of potassium bis(oxalato)palladate(II) dihydrate, [K₂Pd(ox)₂]·2H₂O, with the mentioned organic compounds (H₂ox = oxalic acid; x = 0 for 1-3 and 5 or 2 for 4). Elemental analyses (C, H, N), FTIR, Raman and NMR (¹H, ¹³C, ¹⁵N) spectroscopies, conductivity measurements and thermal studies (thermogravimetric and differential thermal analyses, TG/DTA) have been used to characterize the prepared complexes. The molecular structures of [Pd(L²)₂(ox)] (2) and [Pd(L⁵)₂(ox)]·L⁵·Me₂CO (5·L⁵·Me₂CO) have been determined by a single crystal X-ray analysis. The geometry of these complexes is slightly distorted square-planar with two appropriate Lⁿ (n = 2 or 5) molecules mutually arranged in the head-to-head (2) or head-to-tail (5) orientation. The Lⁿ ligands are coordinated to the central Pd(II) ion via the N7 atoms. The same conclusions regarding the binding properties of L¹-L⁵ ligands can be made based on multinuclear NMR spectra. In vitro cytotoxicity of the complexes 1-5 has been evaluated against human chronic myelogenous leukaemia (K562) and human breast adenocarcinoma (MCF7) cancer cell lines. Significant cytotoxicity has been determined for the complexes 3 (IC₅₀ = 6.2 μM) and 5 (IC₅₀ = 6.8 μM) on the MCF7 cell line, which is even better than that found for the well-known and widely-used platinum-bearing antineoplastic drugs, i.e. oxaliplatin and cisplatin.     

Potential tridentate salicylaldehyde hydrazone of arylalkanoic acid coordinate to copper(II) acting as dinegative tetradentate ligands

A chiral Schiff base N-(S)-2-(6-methoxylnaphthyl)-propanoyl-N′-(2-hydroxylbenzylidene)hydrazine (H₂L) has been synthesized. Reaction of H₂L with Cu(OAc)₂ · H₂O led to the formation of a metal complex {[CuL] · H₂O · 2DMF}_∞ (1). In complex 1, the potential dinegative tridentate L²⁻ ligand acting as tetradentate bridging ligand coordinate to two metal ions so as to form a novel infinite metal-organic coordination chain structure. The enantiomerically pure ligand H₂L presents two different sets of signals in the ¹H NMR spectrum either in chloroform solution or in dimethylsulfoxide solution, showing the presence of both (E) and (Z) isomers. The X-ray structural investigations of H₂L revealed that it is the fully extended E-configuration in the solid state.     

Synthesis, characterization, and cytotoxicity of trimethylplatinum(IV) complexes with 2-thiocytosine and 1-methyl-2-thiocytosine ligands

The reaction of [PtMe₃(MeOH)(bpy)][BF₄] (1) with the thionucleobases 2-thiocytosine (SCy, 2) and 1-methyl-2-thiocytosine (1-MeSCy, 3) resulted in the formation of the complexes [PtMe₃(bpy)(SCy-κS)][BF₄] (4) and [PtMe₃(bpy)(1-MeSCy-κS)] [BF₄] (5), respectively. The complexes were characterized by ¹H and ¹³C NMR spectroscopy as well as by single-crystal X-ray analyses of 4 · MeOH and 5. In 4 · MeOH two strong hydrogen bonds (N4-H?N3′: N4?N3′ 2.976(7) Å) between the thiocytosine ligands give rise to base pairing thus forming dinuclear cations [{PtMe₃(bpy)(SCy-κS)}₂]²⁺. In both complexes the platinum atom is octahedrally coordinated [PtC₃N₂S] by three methyl ligands, the 2,2′-bipyridine ligand and the κS coordinated nucleobase (configuration index: OC-6-33). The structural investigations gave evidence that the sulfur atoms of the nucleobase ligands in 4 · MeOH and 5 have to be regarded as sp³ and sp² hybridized, respectively. Thus, the ligand in 4 · MeOH has to be considered as the deprotonated thiol-amino form of thiocytosine being reprotonated at N1. In complex 5 the 1-MeSCy is coordinated in its thione-amino form. DFT-calculations of the base-paired dinuclear cation in 4 as well as of 4 itself gave proof of the strength of the hydrogen bond (8.5 kcal/mol) and exhibited that cation-anion interactions influence the conformation of the complex. In vitro cytotoxicity studies of 4 and 5 using nine different human tumor cell lines revealed moderate cytotoxic activity.     

Palladium(II) oxalato complexes involving N6-(benzyl)-9-isopropyladenine-based N-donor carrier ligands: Synthesis, general properties, H, C and N{H} NMR characterization and in vitro cytotoxicity

Reactions of potassium bis(oxalato)palladate dihydrate, K₂[Pd(ox)₂]·2H₂O, with two molar equivalents of N6-(benzyl)-9-isopropyladenine-based organic molecules (L_1-7), i.e. 2-chloro-N6-(2-methoxybenzyl)-9-isopropyladenine (L₁), 2-chloro-N6-(3-methoxybenzyl)-9-isopropyladenine (L₂), 2-chloro-N6-(3,5-dimethoxybenzyl)-9-isopropyladenine (L₃), 2-(1-ethyl-2-hydroxyethylamino)-N6-(benzyl)-9-isopropyladenine (L₄), 2-(1-ethyl-2-hydroxyethylamino)-N6-(2-methoxybenzyl)-9-isopropyladenine (L₅), 2-(1-ethyl-2-hydroxyethylamino)-N6-(3-methoxybenzyl)-9-isopropyladenine (L₆) and 2-(1-ethyl-2-hydroxyethylamino)-N6-(4-methoxybenzyl)-9-isopropyladenine (L₇), provided a series of seven palladium(II) oxalato (ox) complexes of the general formula [Pd(ox)(L_1-7)₂]·nH₂O (1-7; n = 0 for 4, 5 and 7, ¾ for 1 and 2, 1 for 6, and 3 for 3). The compounds were characterized by elemental analysis, IR, Raman, ¹H, ¹³C and ¹⁵N{¹H} NMR spectroscopy, ESI+ mass spectrometry, molar conductivity and TG/DTA thermal analysis. The geometry of [Pd(ox)(L₂)₂] (2) was optimized on the B3LYP/6-311G∗/LANL2DZ level of theory. The complexes 4-7 represent the first palladium(II) oxalato complexes with a PdN₂O₂ donor set, which involve highly potent purine-based cyclin-dependent kinase (CDK) inhibitors (L_4-7) as carrier N-donor ligands. The selected complexes 1, 3-5 and 7 were tested by an MTT assay for their in vitro cytotoxic activity against human osteosarcoma (HOS) cancer cell line. The highest activity was found for the complexes 5 (IC₅₀ = 34.9 μM) and 7 (IC₅₀ = 39.2 μM).     

Syntheses, structures, and mesomorphism of a series of Ni(II) salen complexes with 4-substituted long alkoxy chains

A series of nickel(II) salen complexes containing 4-substituted alkoxy chains of aromatic rings, [Ni((4-C_nH_2n + 1O)₂salen)] (n = 3 (1), 4 (2), 6 (3), 8 (4), 10 (5), 12 (6), 14 (7), 16 (8), 18 (9), and 20 (10)), and their parent complex, [Ni((4-HO)₂salen)] (11) (salen = N,N′-ethylenebis(salicylideneiminato)), have been prepared and mesomorphic properties have been investigated. An X-ray crystallographic analysis revealed that complex 11 · 2DMF has one-dimensional stacking structure supported by the π-π interaction between the six-membered chelate and aromatic rings with the NiNi distances of alternatively 3.3957 and 3.7224 Å and that complex 3 is formed by one-dimensional stacking by weak CH?O type hydrogen bonded interaction between the five-membered chelate ring and phenoxo atoms of the dramatically distorted salen moieties with the NiNi distance of 5.994 Å. Complexes 1-6 did not exhibit any mesophases. On the other hand, complexes 7-10 with longer alkoxy chains of n = 14-20 showed an unusual metallomesogen of a lamello-columnar mesophase within the smectic layers with an interlamellar distance of 31.1 Å (7), 33.6 Å (8), 37.1 Å (9), and 39.5 Å (10) and nearly constant stacking distance of 6.19-6.24 Å between the inter-dimers, irrespective of the variation of the alkoxy chain lengths by the X-ray diffraction measurements of the liquid crystal. The relationship between molecular assemblies and mesomorphic properties is discussed.     

Reaction of [MCl2(CH3CN)2] (M = Pd(II), Pt(II)) compounds with N1-alkylpyridylpyrazole-derived ligands

Palladium(II) and platinum(II) complexes with N-alkylpyridylpyrazole-derived ligands, 2-(1-ethyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L¹) and 2-(1-octyl-5-phenyl-1H-pyrazol-3-yl)pyridine (L²), cis-[MCl₂(L)] (M = Pd(II), Pt(II)), have been synthesised. Treatment of [PdCl₂(L)] (L = L¹, L²) with excess of ligand (L¹, L²), pyridine (py) or triphenylphosphine (PPh₃) in the presence of AgBF₄ and NaBPh₄ produced the following complexes: [Pd(L)₂](BPh₄)₂, [Pd(L)(py)₂](BPh₄)₂ and [Pd(L)(PPh₃)₂](BPh₄)₂. All complexes have been characterised by elemental analyses, conductivity, IR and NMR spectroscopies. The crystal structures of cis-[PdCl₂(L²)] (2) and cis-[PtCl₂(L¹)] (3) were determined by a single crystal X-ray diffraction method. In both complexes, the metal atom is coordinated by one pyrazole nitrogen, one pyridine nitrogen and two chlorine atoms in a distorted square-planar geometry. In complex 3, π-π stacking between pairs of molecules is observed.     

Antineoplastic unsaturated fatty acids from Fijian macroalgae

Phytochemical analysis of Fijian populations of the green alga Tydemania expeditionis led to the isolation of two unsaturated fatty acids, 3(ζ)-hydroxy-octadeca-4(E),6(Z),15(Z)-trienoic acid (1) and 3(ζ)-hydroxy-hexadeca-4(E),6(Z)-dienoic acid (2), along with the known 3(ζ)-hydroxy-octadeca-4(E),6(Z)-dienoic acid (4). Investigations of the red alga Hydrolithon reinboldii led to identification of a glycolipid, lithonoside (3), and five known compounds, 15-tricosenoic acid, hexacosa-5,9-dienoic methyl ester, β-sitosterol, 10(S)-hydroxypheophytin A, and 10(R)-hydroxypheophytin A. The structures of 1-3 were elucidated by spectroscopic methods (1D and 2D NMR spectroscopy and ESI-MS). Compounds 1, 2, and 4, containing conjugated double bonds, demonstrated moderate inhibitory activity against a panel of tumor cell lines (including breast, colon, lung, prostate and ovarian cells) with IC₅₀ values ranging from 1.3 to 14.4 μM. The similar cell selectivity patterns of these three compounds suggest that they might act by a common, but unknown, mechanism of action.     

Synthesis, structures, luminescence/magnetic properties of complexes of the M/1-hydroxybenzotriazole, M = cobalt, nickel, silver, zinc and copper

Five novel complexes, Co(OBt)₂ · 7H₂O (1) (OBt = 1-hydroxybenzotriazole ion), Ni₃(OBt)₆ · 6H₂O (2), [Ag(OBt)(HOBt)]_n (3), [Zn(OBt)₂]_n (4) and [Cu₂(OBt)₄ · 3H₂O]_n (5) were synthesized by hydrothermal method and characterized by elemental analysis, IR spectroscopy, TGA, XRPD, and single-crystal X-ray diffraction. The results from single-crystal X-ray diffraction indicate that 1-5 are zero-dimensional (0D), zero-dimensional, one-dimensional (1D), and three-dimensional (3D) frameworks, respectively. In particular, 3 is twin crystal; 4 possesses of double-stranded chains; 5 crystallizes in orthorhombic space group P2₁2₁2₁ with a helical chain in its structure. The luminescence properties and the magnetic properties of the five complexes were investigated.     

Cholinergic and neuroprotective drugs for the treatment of Alzheimer and neuronal vascular diseases. II. Synthesis, biological assessment, and molecular modelling of new tacrine analogues from highly substituted 2-aminopyridine-3-carbonitriles

The synthesis, biological assessment, and molecular modelling of new tacrine analogues 11-22 is described. Compounds 11-22 have been obtained by Friedländer-type reaction of 2-aminopyridine-3-carbonitriles 1-10 with cyclohexanone or 1-benzyl-4-piperidone. The biological evaluation showed that some of these molecules were good AChE inhibitors, in the nanomolar range, and quite selective regarding the inhibition of BuChE, the most potent being 5-amino-2-(dimethylamino)-6,7,8,9-tetrahydrobenzo[1,8-b]-naphthyridine-3-carbonitrile (11) [IC₅₀ (EeAChE: 14 nM); IC₅₀ (eqBuChE: 5.2 ??M]. Kinetic studies on the easily available and potent anticholinesterasic compound 5-amino-2-(methoxy)-6,7,8,9-tetrahydrobenzo[1,8-b]-naphthyridine-3-carbonitrile (16) [IC₅₀ (EeAChE: 64 nM); IC₅₀ (eqBuChE: 9.6 ??M] showed that this compound is a mixed-type inhibitor (K_i = 69.2 nM) of EeAChE. Molecular modelling on inhibitor 16 confirms that this compound, as expected and similarly to tacrine, binds at the catalytic active site of EeAChE. The neuroprotective profile of molecules 11-22 has been investigated in SH-SY5Y neuroblastoma cells stressed with a mixture of oligomycin-A/rotenone. Compound 16 was also able to rescue by 50% cell death induced by okadaic acid in SH-SY5Y cells. From these results we conclude that the neuroprotective profile of these molecules is moderate, the most potent being compounds 12 and 17 which reduced cell death by 29%. Compound 16 does not affect ACh- nor K⁺-induced calcium signals in bovine chromaffin cells. Consequently, tacrine analogues 11-22 can be considered attractive therapeutic molecules on two key pharmacological targets playing key roles in the progression of Alzheimer, that is, cholinergic dysfunction and oxidative stress, as well as in neuronal cerebrovascular diseases.